Identification and Treatment Of Unstable Plaque with OCT

描述（由申请人提供）：该项目是NIH R01 EB002638（原NIH R01 HL63953）“提高光学相干断层扫描易损斑块评估的诊断潜力”的竞争延续。这项工作的长期目标是开发一种新的高分辨率血管内成像方法，以克服目前心脏诊断的局限性，主要是识别可能导致急性冠脉综合征（即心肌梗死或不稳定型心绞痛）的冠状动脉斑块。大多数急性冠脉综合征（ACS）是由冠状动脉小斑块破裂而不是大斑块破裂引起的。这些易损斑块最典型的是薄帽纤维动脉粥样瘤（TCFA），它含有相对大量的复杂坏死核心，具有高浓度的脂质和出血，以及覆盖在其上的薄胶原蛋白耗尽的内膜帽。当这些斑块破裂时，它们释放血栓形成物质进入血液，形成血栓，血管经常闭塞。这些小斑块超出了目前任何可用的成像方式的检测范围。光学相干断层扫描（OCT）是一种新的高分辨率成像方法，在评估不稳定斑块方面显示出巨大的潜力。部分通过NIH RO1 HL55686和R01 HL63953/ EB002638生成的初步数据强烈提示OCT用于易损斑块评估的可行性。10缸的分辨率允许对动脉内的微观结构进行前所未有的定义。由于OCT现在被引入体内人体成像，允许识别一些TCFA，一个重要的问题出现了。大多数ACS是由TCFA引起的，但大多数TCFA不是导致ACS的原因。虽然OCT可以识别内膜帽小于70毫米的斑块，这比其他成像方式有很大的进步，但除了TCFA的识别之外，OCT还需要进一步对这些斑块进行风险分层，这是目前最先进的技术。如果该领域在21世纪继续取得进展，就必须关注具有易形成血栓病变的高危患者，以及导致斑块在精确位置和时间破裂的触发机制。本提案的假设是，OCT技术可以通过辅助技术的发展来提高薄帽动脉粥样硬化的风险分层，识别导致急性冠状动脉综合征的因素。该假设将通过技术的进步、体外人冠状动脉的评估、体外红细胞注射（出血性）动脉粥样硬化兔子斑块的成像（目前产生斑块最接近人类TCFA的大型动物模型）、兔动脉粥样硬化斑块的体内成像以及监测治疗引起的体内变化来验证。此外，我们将同时尝试通过诱导血管生成来进一步改进兔出血性斑块模型，血管生成可能最终是许多斑块破裂的触发因素。

DESCRIPTION (provided by applicant): This program is a competing continuation of NIH R01 EB002638 (formerly NIH R01 HL63953) "Improving the Diagnostic Potential of Optical Coherence Tomography for Vulnerable Plaque Assessment". The long- term objective of this work is to develop a new method of high resolution intravascular imaging to overcome current limitations in cardiac diagnostics, principally the identification of coronary plaques likely to lead to acute coronary syndromes (i.e. myocardial infarction or unstable angina). Most acute coronary syndromes (ACS) result from the rupture of small rather than large plaques in the coronary arteries. These vulnerable plaques are most typically thin cap fibroatheromas (TCFA) that contain a relatively large amount of complex necrotic core with a high concentration of lipid and hemorrhage, and an overlying thin collagen-depleted, intimal cap. When these plaques rupture, they release thrombogenic material into the blood, a clot forms, and the vessel frequently occludes. These small plaques are beyond the detection limit of any currently available imaging modalities. Optical coherence tomography (OCT), a new method of high resolution imaging, has demonstrated great potential for the assessment of unstable plaques. Preliminary data, generated in part through NIH RO1 HL55686 and R01 HL63953/ EB002638, has strongly suggested a feasibility of OCT for vulnerable plaque assessment. The 10 urn resolution allowed unprecedented definition of microstructure within arteries. As OCT is now being introduced for in vivo human imaging, allowing the identification of some TCFA, an important concern arises. Most ACS result from TCFA, but most TCFA do not lead to ACS. While OCT can identify plaques with intimal caps less than 70 urn, a substantial advance over other imaging modalities, a need exists for OCT to further risk stratify these plaques beyond the identification of TCFA, which is the current state of the art. If progress inthe field is to continue in the 21 st century, one must focus on high-risk patients with lesions that are vulnerable to thrombosis together with the triggering mechanisms that cause plaques to rupture at a precise location and time. The hypothesis of this proposal is that OCT technology can be advanced through the development of adjuvant technologies to improve risk stratification of thin cap atheromas, identifying those which lead to acute coronary syndromes. The hypothesis will be tested with advancements of the technology, assessment of in vitro human coronary arteries, imaging of in vitro RBC injected (hemorrhagic) atherosclerotic rabbit plaque (the current large animal model producing plaques most closely resembling human TCFA), in vivo imaging of rabbt atherosclerotic plaque, and monitoring in vivo changes induced with therapeutics. In addition, we will in parallel attempt to further improve the rabbit hemorrhagic plaque model by inducing angiogenesis, the factor which may ultimately be the trigger of many plaque ruptures.